4-(4-Bromophenyl)-1-[3-(11-cyano-6,11-dihydrodibenzo[b,e]thiepin-11-yl)propyl]piperidin-4-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫平类
• 英文名称: 4-(4-Bromophenyl)-1-[3-(11-cyano-6,11-dihydrodibenzo[b,e]thiepin-11-yl)propyl]piperidin-4-ol
• 英文别名: 11-[3-[4-(4-Bromophenyl)-4-hydroxy-1-piperidinyl]propyl]-6,11-dihydrodibenzo[b,e]thiepin-11-carbonitrile；11-[3-[4-(4-bromophenyl)-4-hydroxypiperidin-1-yl]propyl]-6H-benzo[c][1]benzothiepine-11-carbonitrile
• 化学式: C₂₉H₂₉BrN₂OS
• 分子量: 533.532
• InChiKey: XJLAHAKPPWTBRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  72.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  11-(2-bromopropyl)-6,11-dihydrodibenzothiepin-11-carbonitrile 、 4-(4-溴苯基)-4-哌啶醇 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以73%的产率得到4-(4-Bromophenyl)-1-[3-(11-cyano-6,11-dihydrodibenzo[b,e]thiepin-11-yl)propyl]piperidin-4-ol
  参考文献：
  名称：

  发现新型非肽CCR1受体拮抗剂。

  摘要：

  CCR1受体的配体（MIP-1alpha和RANTES）与多种慢性炎症性疾病有关，最明显的是多发性硬化症和类风湿关节炎。由于这些配体共享一个共同的受体CCR1，因此我们寻求发现该受体的拮抗剂作为治疗这些疾病的一种方法。通过高通量筛选（HTS）已经发现了一系列新型的4-羟基哌啶，其有效抑制了MIP-1α和RANTES与重组人CCR1趋化因子受体的结合。该模板各部分的结构活性关系被描述为：最初的HTS导联1已通过合成优化为高效受体拮抗剂6s。与其他人类7-TM受体相比，该化合物对CCR1的抑制作用具有至少200倍的选择性，包括其他趋化因子受体。此外，从体外功能测定中获得的数据证明了化合物6s和与结构相关的类似物对CCR1受体的功能拮抗作用具有浓度依赖性。以化合物6s为代表的有效和选择性CCR1受体拮抗剂的发现和优化可能代表了一种治疗慢性炎性疾病的新方法。

  DOI：

  10.1021/jm990316l

文献信息

• Methods of Inhibiting Metastasis from Cancer
  申请人：Salvino Joseph M.

  公开号：US20120141471A1

  公开（公告）日：2012-06-07

  The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX 3 CR1 or fractalkine antagonist.

  本发明涉及一种用于预防或治疗被诊断为癌症的患者中的转移的组合物。本发明还包括一种用于预防或治疗被诊断为癌症的患者中的转移的方法，其中该方法包括向需要该药物的患者投与至少一种药用制剂，该制剂包括至少一种药用载体和至少一种CX3CR1或fractalkine拮抗剂的有效量。
• Chemokine receptor antagonists and methods of use therefor
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20020151553A1

  公开（公告）日：2002-10-17

  Disclosed is a method of treating a subject with a disease associated with aberrant leukocyte recruitment and/or activation. The method comprises administering to the subject a therapeutically effective amount of a compound represented by the following structural formula: 1 and physiologically acceptable salts thereof. Z is a cycloalkyl or non-aromatic heterocyclic ring group fused to one or more carbocyclic aromatic rings and/or heteroaromatic rings, wherein each ring in Z is independently substituted or unsubstituted; Y is a covalent bond, —O— or —CO—; n is an integer from one to about five; X is a covalent bond or —CO—; and M is >NR 2 , >CR 1 R 2 ; R 1 is —H, —OH, an aliphatic group, —O—(aliphatic group), —SH or —S—(aliphatic group); R 2 is an aliphatic group, a substituted aliphatic group, an aromatic group, a substituted aromatic group, a benzylic group, a substituted benzylic group, a non-aromatic heterocyclic group or a substituted non-aromatic heterocyclic group.

  本发明涉及一种治疗与异常白细胞招募和/或激活相关的疾病的方法。该方法包括向患者投与以下结构式所表示的化合物的治疗有效量及其生理上可接受的盐：1 其中，Z是一个环烷基或非芳香族杂环环基，与一个或多个碳环芳香族环和/或杂环芳香族环融合，其中Z中的每个环都是独立取代或未取代的；Y是共价键，-O-或-CO-；n是从1到约5的整数；X是共价键或-CO-；M是> NR2，> CR1R2；R1是-H，-OH，脂肪基，-O-（脂肪基），-SH或-S-（脂肪基）；R2是脂肪基，取代脂肪基，芳香族基，取代芳香族基，苄基，取代苄基，非芳香族杂环基或取代非芳香族杂环基。
• Compounds Useful for Inhibiting Metastasis from Cancer and Methods Using Same
  申请人：Drexel University College of Medicine Philadelphia Health & Education Corporation d/b/a

  公开号：US20130156761A1

  公开（公告）日：2013-06-20

  The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX 3 CR1 or fractalkine antagonist.

  本发明涉及一种对已被诊断患有癌症的受试者预防或治疗转移的有用组合物。本发明还涉及一种预防或治疗已被诊断患有癌症的受试者的转移的方法，其中该方法包括向需要该药物的受试者施用至少一种药物制剂，该药物制剂包括至少一种药用载体和至少一种CX3CR1或fractalkine拮抗剂的有效量。
• Compounds useful for inhibiting metastasis from cancer and methods using same
  申请人：Drexel University

  公开号：US10414771B2

  公开（公告）日：2019-09-17

  The present invention includes compositions that are useful in preventing or treating metastasis in a subject diagnosed with cancer. The present invention also includes methods of preventing or treating metastasis in a subject diagnosed with cancer, wherein the method comprises administering to the subject in need thereof an effective amount of a pharmaceutical formulation comprising at least one pharmaceutically acceptable carrier and at least one CX3CR1 or fractalkine antagonist.

  本发明包括可用于预防或治疗确诊癌症患者转移的组合物。本发明还包括预防或治疗被诊断患有癌症的受试者的转移的方法，其中该方法包括向需要该方法的受试者施用有效量的药物制剂，该药物制剂包含至少一种药学上可接受的载体和至少一种CX3CR1或fractalkine拮抗剂。
• US6323206B1
  申请人：——

  公开号：US6323206B1

  公开（公告）日：2001-11-27